Fig 1.
Structures of compounds isolated from the lichen S. evolutum and of the semi-synthetic compounds 5–6.
Table 1.
NMR data for compound 2 in DMSO-d6 (400 MHz for 1H and 100 MHz for 13C).
Fig 2.
HMBC key correlations for compound 2.
Fig 3.
Compound 2 (extracted at Rt = 19.48 min) was detected through PDA chromatograms (total scan at λ = 220–600 nm), base-peak mass chromatograms and MS spectra of extemporaneously prepared acetone extract of S. evolutum (a), an ethyl acetate extract of S. evolutum (b) and pure atranorin macerated in acetone for one week (c).
Table 2.
Anti-HCV activity and toxicity of atranorin derivativesa.
Fig 4.
Effects of compounds 1, 5 and 6 on cell viability and HCV propagation in vitro.
One day after seeding at 50,000 cells/cm2, Huh-7.5.1 cells were infected with HCVcc at a MOI ~ 0.03 for 17 h (inoculation phase: I). The inoculum was removed and cell cultures were washed before the addition of new medium and incubation for an additional 30 h (replication phase: R). Compounds were present at various concentrations either during both phases (I/R: black circles and solid lines) or during only one phase (I: black squares and dotted lines; R: black triangles and dashed lines). (A) Cell viability and (B) viral replication were assessed at the end of the incubation period. Results are expressed as percentages (mean ± SEM; n = 3) of the mean values obtained for the respective control cultures, in which cells were incubated with vehicle (0.1% DMSO) alone. Erlotinib and telaprevir were used as positive antiviral drug controls inhibiting the entry and replication steps, respectively.